Adults older than 65 years are at increased risk for atypical presentations of chikungunya disease, as well as for severe outcomes including death.

Ageing is a scientifically fascinating and complex biological occurrence characterised by morphological and functional changes due to accumulated molecular and cellular damage impairing tissue and organ function. Ageing is often accompanied by cognitive decline but is also the biggest known risk factor for Alzheimer's disease, the most common form of dementia. Emerging evidence suggests that sedentary and unhealthy lifestyles accelerate brain ageing, while regular physical activity, high cardiorespiratory fitness (CRF), or a combination of both, can mitigate cognitive impairment and reduce dementia risk. The purpose of this Review is to explore the neuroprotective mechanisms of endurance exercise and highlight the importance of CRF in promoting healthy brain ageing. Key findings show how CRF mediates the neuroprotective effects of exercise via mechanisms such as improved cerebral blood flow, reduced inflammation, and enhanced neuroplasticity. We summarise evidence supporting the integration of endurance exercise that enhances CRF into public health initiatives as a preventive measure against age-related cognitive decline. Additionally, we address important challenges such as lack of long-term studies with harmonised study designs across preclinical and clinical settings, employing carefully controlled and repeatable exercise protocols, and outline directions for future research.

Overactive bladder is a common problem affecting women worldwide, with a negative effect on their social and professional lives. Before considering invasive treatments, guidelines recommend urodynamics to identify detrusor overactivity. However, the clinical-effectiveness and cost-effectiveness of urodynamics has never been robustly assessed in this cohort of women. We aimed to compare the clinical-effectiveness and cost-effectiveness of urodynamics plus comprehensive clinical assessment (CCA) versus CCA only in the management of women with refractory overactive bladder symptoms.

Almost 40 years ago, the discovery of the vasoactive neuropeptide calcitonin gene-related peptide (CGRP) and its role in migraine pathophysiology ushered in a new era in migraine treatment. Since 2018, monoclonal antibodies (mAbs) targeting the CGRP pathway are available for migraine prevention. The approval of these drugs marks a pioneering development, as they are the first pharmacological agents specifically tailored for migraine prevention. Introduction of these agents contrasts the historical reliance on traditional preventive medications initially formulated for other indications and later repurposed for migraine therapy. Although the emergence of evidence on the efficacy and safety of CGRP-targeted mAbs has raised the bar for treatment success in migraine, their efficacy in other headache entities, such as cluster headache, is low to moderate. Small-molecule CGRP receptor antagonists called gepants have also been proven to be effective both as acute and preventive migraine treatments. Furthermore, these agents have bridged the traditional categories of acute and preventive treatment strategies. Short-term prevention and treatment during the prodromal phase of migraine represent emerging strategies enabling clinicians to develop treatment approaches designed to meet changing patient needs; however, these strategies still require more formal evidence. Although solid data have been gathered, further research concerning the efficacy and long-term safety of drugs targeting the CGRP pathway and robust pharmacoeconomic evaluations are needed. Finally, randomised withdrawal and switching studies would facilitate the formulation of evidence-based guidance for the discontinuation of and switching between drugs targeting the CGRP pathway.

Despite a substantial reduction in the use of solid fuels for cooking worldwide, exposure to household air pollution (HAP) remains a leading global risk factor, contributing considerably to the burden of disease. We present a comprehensive analysis of spatial patterns and temporal trends in exposure and attributable disease from 1990 to 2021, featuring substantial methodological updates compared with previous iterations of the Global Burden of Diseases, Injuries, and Risk Factors Study, including improved exposure estimations accounting for specific fuel types.

Human African trypanosomiasis or sleeping sickness is caused by infection with Trypanosoma brucei gambiense or Trypanosoma brucei rhodesiense parasites, which are transmitted by tsetse flies in sub-Saharan Africa. Control of human African trypanosomiasis is based on case detection, treatment, and vector control. In the past decade, simple rapid diagnostic tests were introduced for gambiense human African trypanosomiasis, facilitating screening in primary health-care facilities. A new oral drug, fexinidazole, became the first-line treatment for gambiense human African trypanosomiasis without severe meningo-encephalitic disease, as well as for rhodesiense human African trypanosomiasis. Medical interventions, in some areas combined with tiny target-based vector control, have substantially reduced human African trypanosomiasis incidence, despite temporary disruptions to health-care systems. The elimination of human African trypanosomiasis as a public health problem has been achieved, and elimination of gambiense human African trypanosomiasis transmission is now targeted for 2030. Improved diagnostics and drugs, continued involvement of populations at risk of disease, health staff, national authorities, and partners and donors all contribute to achieve this goal.

Uptake of colorectal cancer screening is suboptimal. The TEMPO trial evaluated the impact of two evidence-based, theory-informed, and co-designed behavioural interventions on uptake of faecal immunochemical test (FIT) colorectal screening.

Invasive meningococcal disease is a devastating public health problem for the African meningitis belt. We assessed the safety and immunogenicity of a pentavalent meningococcal conjugate vaccine targeting serogroups A, C, Y, W, and X (NmCV-5) relative to a licensed, quadrivalent meningococcal conjugate vaccine (MenACWY-TT) when co-administered with routine childhood vaccines at ages 9 months and 15 months.

Long-acting antiretrovirals can address barriers to HIV pre-exposure prophylaxis (PrEP), such as stigma and adherence. In two phase 3 trials, twice-yearly subcutaneous lenacapavir was safe and highly efficacious for PrEP in diverse populations. Furthering long-acting PrEP efforts, this study assessed the pharmacokinetics and safety of two once-yearly intramuscular lenacapavir formulations.

The impact of digital adherence technologies on tuberculosis treatment outcomes remains poorly understood. We investigated whether smart pillboxes and medication labels can reduce poor treatment outcomes in patients with tuberculosis.

Brain infections pose substantial challenges in diagnosis and management and carry high mortality and morbidity, especially in low-income and middle-income countries. We aimed to improve the diagnosis and early management of patients admitted to hospital (adults aged 16 years and older and children aged >28 days) with suspected acute brain infections at 13 hospitals in Brazil, India, and Malawi.

Tuberculosis is a leading cause of death globally. Given the airborne transmission of tuberculosis, anybody can be infected, but people in high-incidence settings are more exposed. Risk of progression to disease is higher in the first years after infection, and in people with undernourishment, immunosuppression, or who smoke, drink alcohol, or have diabetes. Although cough, fever, and weight loss are hallmark symptoms, people with tuberculosis can be asymptomatic, so a high index of suspicion is required. Prompt diagnosis can be made by sputum examination (ideally with rapid molecular tests), but chest radiography can be helpful. Most people with disease can be treated with regimens of 6 months or less; longer regimens may be necessary for those with drug resistance. Central to successful treatment is comprehensive, person-centred care including addressing key determinants, such as undernourishment, smoking, and alcohol use, and optimising management of comorbidities, such as diabetes and HIV. Care should continue after treatment ends, as long-term sequelae are common. Prevention relies mostly on treatment with rifamycin-based regimens; current vaccines have limited efficacy. Ongoing research on shorter and safer regimens for infection and disease treatment, and simpler and more accurate diagnostic methods will be key for tuberculosis elimination.

Ivonescimab is a bispecific antibody against programmed cell death protein 1 and vascular endothelial growth factor, yielding promising clinical outcomes for patients with advanced non-small cell lung cancer in early-phase studies. We compared the efficacy and safety of ivonescimab with pembrolizumab in patients with programmed cell death ligand-1 (PD-L1)-positive advanced non-small cell lung cancer.

Malaria remains a leading cause of illness and death globally, with countries in sub-Saharan Africa bearing a disproportionate burden. Global high-resolution maps of malaria prevalence, incidence, and mortality are crucial for tracking spatially heterogeneous progress against the disease and to inform strategic malaria control efforts. We present the latest such maps, the first since 2019, which cover the years 2000-22. The maps are accompanied by administrative-level summaries and include estimated COVID-19 pandemic-related impacts on malaria burden.

Tocolytics are recommended in international guidelines as treatment for threatened preterm birth. Atosiban, an oxytocin receptor antagonist, is a registered tocolytic drug specifically indicated for the treatment of threatened preterm birth. Although tocolytics have been shown to delay birth, benefits on neonatal outcomes have not been demonstrated. In the APOSTEL 8 trial we aimed to assess superiority of tocolysis with atosiban compared with placebo in threatened preterm birth from 30 weeks and 0 days (30+0 weeks) to 33+6 weeks of gestation in improving neonatal morbidity and mortality.

Overweight and obesity is a global epidemic. Forecasting future trajectories of the epidemic is crucial for providing an evidence base for policy change. In this study, we examine the historical trends of the global, regional, and national prevalence of adult overweight and obesity from 1990 to 2021 and forecast the future trajectories to 2050.

Despite the well documented consequences of obesity during childhood and adolescence and future risks of excess body mass on non-communicable diseases in adulthood, coordinated global action on excess body mass in early life is still insufficient. Inconsistent measurement and reporting are a barrier to specific targets, resource allocation, and interventions. In this Article we report current estimates of overweight and obesity across childhood and adolescence, progress over time, and forecasts to inform specific actions.

Chronic rhinosinusitis with nasal polyps (CRSwNP) symptoms are frequently driven by type 2 inflammation. Depemokimab is the first ultra-long-acting biological drug engineered with enhanced interleukin-5 binding affinity, high potency, and an extended half-life, enabling twice per year dosing and sustained type 2 inflammation inhibition. The ANCHOR-1 and ANCHOR-2 trials investigated the efficacy and safety of depemokimab in people with CRSwNP.

The WHO Global Oral Health Action Plan has set an overarching global target of achieving a 10% reduction in the prevalence of oral conditions by 2030. Robust and up-to-date information on the global burden of oral conditions is paramount to monitor progress towards this target. The aim of this systematic data analysis was to produce global, WHO region, and country-level estimates of the prevalence of, and disability-adjusted life-years (DALYs) attributed to, untreated caries, severe periodontitis, edentulism, other oral disorders, lip and oral cavity cancer, and orofacial clefts from 1990 to 2021.

Haemophilia A and B are congenital X-linked bleeding disorders resulting from deficiencies in clotting factors VIII (haemophilia A) and IX (haemophilia B). Patients with severe deficiency, defined as having less than 1% of normal plasma factor activivity, often have spontaneous bleeding within the first few years of life. Those with moderate and mild deficiencies typically present with post-traumatic or post-surgical bleeding later in life. A high index of suspicion and measurement of factor activity in plasma facilitates early diagnosis. In the 21st century, therapeutic advances and comprehensive care have substantially improved both mortality and morbidity associated with these conditions. Management strategies for haemophilia include on-demand treatment for bleeding episodes and all surgeries and regular treatment (ie, prophylaxis) aimed at reducing bleeds, morbidity, and mortality, thereby enhancing quality of life. Treatment options include factor replacement therapy, non-replacement therapies that increase thrombin generation, and gene therapies that facilitate in vivo clotting factor synthesis. The therapies differ in their use for prophylaxis and on-demand treatment, the mode and frequency of administration, duration of treatment effect, degree of haemostatic protection, and side-effects. Monitoring the effectiveness of these prophylactic therapies involves assessing annual bleeding rates and joint damage. Personalised management strategies, which align treatment with individual goals (eg, playing competitive sports), initiated at diagnosis and maintained throughout the lifespan, are crucial for optimal outcomes. These strategies are facilitated by a multidisciplinary team and supported by clinician-led education for both clinicians and patients.